It is the goal of this study to determine how tumor promoters modulate phosphorylation of growth hormone receptors in order to understand how tumor promoters influence membrane properties, stimulate cell growth, and ultimately, act as promoters in carcinogenesis. Monoclonal antibodies directed against phosphotyrosine residues will be used as a selective probe for isolation of proteins of interest. Having shown that tumor promoters (both phorbol and nonphorbol) inhibit EGF-induced phosphorylation of the epidermal growth factor (EGF) receptor, our major focus is to characterize the nature of the inhibitory response. The information gained would provide an understanding of the regulation of the phosphorylation event induced by EGF and may be applicable as a screen for certain classes of tumor promoters. Further, we will determine whether tumor promoters modulate growth hormone-induced phosphorylation of cell surface receptors in non-EGF systems, such as platelet-derived growth factor and transforming growth factors. Since phosphorylation of tyrosine residues has been implicated as an initial event in the process of hormone-induced mitogenesis, an understanding of the factors which regulate this step would also provide valuable information regarding the mechanism of mitogenic stimulation.